Ethanol and Murine Interleukin (IL)-12 Production

Abstract

Interleukin (IL)-12 is a cytokine with protean effects against bacterial and intracellular pathogens. Induction of IL-12 at the time of infection has salient effects on elimination of various microbes. This work describes the effect of exposure to ethanol on lipopolysaccharide (LPS)-induced production of IL-12 in mice and whether ethanol-induced increases in IL-10 mediates these changes in IL-12 production. BALB/c mice were pretreated with ethanol and then challenged with LPS either intravenously (iv) or intratracheally (it), and blood and lung production of IL-12 (p70 and p40 components) and serum IL-10 were assayed. Splenic and lung mRNA for IL-12 p35 and p40 components was determined. Ethanol pretreatment suppressed LPS-induced IL-12 p70 and p40 protein production in blood and lung. In spleen and lung, p40 mRNA was induced to a greater extent than p35 mRNA, and there was greater suppression of p40 mRNA compared with p35 mRNA in ethanol-treated animals. Ethanol up-regulated the production of IL-10, and pretreatment of these animals with a polyclonal anti-IL-10 antibody resulted in significant increases in IL-12 p70 and p40 levels, but not completely to those of control animals. Ethanol suppresses the production of murine IL-12 in response to LPS in blood and lung, with both the p70 and the p40 components affected. This suppression is accompanied by reductions of p40 mRNA in both spleen and lung. IL-10 may play a role in ethanol-induced suppression of IL-12, as neutralization of IL-10 partially attenuated the suppression of IL-12.